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Abstract: TH-PO664

Albuminuria and eGFR in Midlife and Older Age as Risk Factors of Dementia: The ARIC Study

Session Information

  • Geriatric Nephrology
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Geriatric Nephrology

  • 1100 Geriatric Nephrology

Authors

  • Scheppach, Johannes B., Johns Hopkins University, Baltimore, Maryland, United States
  • Coresh, Josef, Welch Center for Prevention, Epidemiology & Clinical Research, Baltimore, Maryland, United States
  • Wu, Aozhou, The Johns Hopkins University, Baltimore, Maryland, United States
  • Gottesman, Rebecca F., Johns Hopkins University, Baltimore, Maryland, United States
  • Mosley, Tom, Univ. of Miss. Med Center, Jackson, Mississippi, United States
  • Grams, Morgan, Johns Hopkins University, Baltimore, Maryland, United States
  • Sharrett, Richey, Johns Hopkins, Baltimore, Maryland, United States
  • Koton, Silvia, Tel Aviv University and Johns Hopkins University, Tel Aviv, Israel
Background

Urine albumin-creatinine-ratio (UACR) and estimated glomerular filtration rate (eGFR) define chronic kidney disease (CKD) and are related to microvascular disease and endothelial damage. We extend previous studies by examining UACR and eGFR measured at midlife and older age as risk factors for dementia. Furthermore, we compare eGFR based on creatinine with eGFR based on cystatin C and beta 2 microglobulin.

Methods

We studied 9,967 participants aged 54-74 years in the Atherosclerosis Risk in Communities (ARIC) study who attended visit 4 (1996-1999) and had creatinine, cystatin C, beta 2 microglobulin and UACR measured with follow-up to December 31st, 2017. We evaluated the hazard of incident dementia associated with eGFR (based on creatinine, cystatin C and beta 2 microglobulin) and log UACR adjusted for age, sex, race, education and apolipoprotein E4 level (Model 1) and additionally for smoking, body mass index, diabetes and antihypertensive medication (Model 2). We compared eGFR and UACR associations to those observed among visit 5 participants (N=4,626, age 70-90, 2011-2013). Effect sizes for each measure of CKD were normalized to the interquartile range (IQR) at Visit 4.

Results

We observed 1,821 incident dementia cases over 16 years of follow-up (438 after visit 5). Risk of dementia was higher with higher levels of albuminuria and lower levels of eGFR but only when GFR estimation was based on cystatin C or beta 2 microglobulin (Table). There was no substantial difference in risk of dementia associated with eGFR or UACR between the two baseline visits.

Conclusion

Higher albuminuria is strongly related to dementia incidence. Lower eGFR shows similar associations but only when the estimation is based on cystatin C or beta 2 microglobulin. This could be explained by newer biomarkers being less influenced by muscle mass. The results are similar in midlife compared to older age.

Measure of CKD
per V4 interquartile range, IQR
Baseline Visit 4, ages 54-74 yearsBaseline Visit 5, ages 70-90 years
Model 1:Model 2:Model 1:Model 2:
eGFR CKD-EPI, creatinine
per 19.4 ml/min decrease
0.98 (0.92 – 1.04)0.98 (0.91 – 1.05)1.11 (0.99 - 1.24)1.03 (0.91 – 1.17)
eGFR CKD-EPI, cystatin C
per 24.3 ml/min decrease
1.16 (1.07 – 1.25)*1.12 (1.03 – 1.21)*1.33 (1.16 - 1.53)*1.23 (1.05 – 1.44)*
eGFR CKD-EPI, creatinine and cystatin C
per 20.7 ml/min decrease
1.08 (1.01 – 1.16)*1.06 (0.98 – 1.14)1.23 (1.09 - 1.38)*1.13 (0.99 – 1.30)
eGFR CKD-EPI, beta 2 microglobulin
per 18.3 ml/min decrease
1.18 (1.11 – 1.27)*1.14 (1.06 – 1.23)*1.36 (1.20 - 1.54)*1.30 (1.12 – 1.50)*
Log urine albumin-creatinine ratio
per 4.2 fold increase
1.19 (1.13 – 1.25)*1.15 (1.09 – 1.21)*1.32 (1.18 - 1.46)*1.32 (1.17 – 1.49)*
Table: Adjusted HRs (95% CIs) for dementia incidence after midlife and after older age, by measure of CKD
Model 1: adjusted for age, sex, race, education and Apolipoprotein E4 level
Model 2: adjusted for age, sex, race, education, Apolipoprotein E4 level, smoking, body mass index, diabetes and antihypertensive medication.
*p < 0.05

Funding

  • Other NIH Support